Predictive value of bevacizumab –related hypertension and proteinuria in patients with mCRC in the real practice

Abstract

Background: The anti-VEGF monoclonal antibody Bevacizumab has shown to prolong both PFS and OS in patients with metastatic colorectal cancer (mCRC) in association with chemotherapy in many randomized trials. Although Bevacizumab - containing first or second therapies are largely administrated, not all pts benefit from it and there are no biomarkers available for the prediction of its efficacy. Several studies demonstrated a connection between hypertension, proteinuria (common side effects of bevacizumab) and improvement of disease outcome in pts with mCRC. Patients and methods: In this study we retrospectively assessed whether treatment-related hypertension and proteinuria are associated with outcome in consecutive mCRC pts treated with bevacizumab at the Oncology Unit of Ferrara before March 2014. Clinical, radiological and laboratory data were available on electronic medical records of our Hospital. We performed an univariate analysis of survival in order to compare TTP and OS between pts developing hypertension or proteinuria and those who have not presented these side effects. Results: We collected data from 61 pts, median age 61 (range 40-75). The site of primitive tumor was colon in 67% and rectum in 33% of pts. KRAS exon 2 (codons 12/13) analysis was performed in 50 pts (37.7% mutated, 43% wild type). The majority of them (77%) received Bevacizumab - containing therapy as first line of treatment while 23% as second line. Eight pts (13%) developed grade 2-4 hypertension during the treatment with bevacizumab after a median period of 8 weeks (range 4-17). All pts received antihypertensive drugs with good control of the adverse event The median TTP was 9 months (95% CI 5.7-12.2) in pts developing hypertension vs 6 months (95% CI 5.1-6.9) in pts without hypertension, p= 0.03 . No association between G2-G4 hypertension and OS was found. A total of 20 pts (33%) had proteinuria during bevacizumab treatment; this was moderate to severe in 6 pts (9%). Proteinuria occurs after a median period of 14 weeks (range 11-25) and was not significantly correlated to TTP and OS in our analysis. Conclusion: Treatment of mCRC with bevacizumab was shown to be well tolerated and easily manageable. Our analysis of the data confirms that the development of hypertension could be a predictive factor for response.